A significant relationship exists between iron nutrition and cognition and behavior. Behavioral problems are also observed in children with high manganese and manganese neurotoxicity resulting in a Parkinson-like disorder that is widely recognized in workers employed in mining and manganese ore processing. Our recent work has established that iron deficiency enhances olfactory uptake of manganese and promotes accumulation of this toxic metal in the basal ganglia. Thus, the major underlying hypothesis of this proposal is that absorption of inhaled manganese is up-regulated upon iron-deficiency such that neurological complications of poor iron status are compounded by an increased vulnerability to the toxic effects of manganese exposure. The proposed research will contribute fundamental understanding of physiological risks associated with metal-induced toxicity and, more specifically, the interactions between iron status and manganese neurotoxicity. To accomplish this goal we will: 1) Determine the distribution of intranasally instilled manganese in the brain of control and iron-deficient rats using magnetic resonance imaging; 2) Determine motor coordination and learning/memory capacity of exposed and non-exposed cohorts through use of rotorod and bridge-walking as well Morris water maze tests; and 3) Examine CNS damage due to manganese intoxication in control and iron-deficient rats by determining indices of oxidative stress (3- nitrotyrosine and 8-hydroxy-2'deoxyguanosine levels), identifying neuronal degeneration (Fluoro-Jade staining) and evaluating astrocyte viability using anti-fibrillary acidic protein (GFAP) and microglia status using anti-isolectin B4. [unreadable] [unreadable] [unreadable]